Study identifies new risk loci for eczema

Press release

Tuesday, October 20th, 2015

Researchers have identified new loci associated with atopic dermatitis by genetic association studies. To identify these new markers of susceptibility loci for this common, complex skin disease, the researchers performed a meta-analysis of more than 15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies.

Atopic dermatitis or eczema is a common inflammatory skin disease affecting 15–30% of children and 5–10% of adults. Its pathogenesis involves abnormalities in the skin barrier and T cell–driven cutaneous inflammation. This disease has considerable genetic contributions, with heritability estimates of up to 90% in Europeans. The strongest known risk factors are null mutations of the FLG gene (encoding filaggrin), which causes deficiencies in epidermal barrier. Genome-wide association studies have identified 20 additional loci (ten in European populations, eight in Japanese populations and two in Chinese populations), mostly implicated in immune dysregulation.

The researchers of this study, published in Nature Genetics, have identified ten new markers of risk, bringing the total number of known atopic dermatitis risk loci to 30. In particular, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

“We have identified ten new loci strongly associated with atopic dermatitis in the European population, six of them with a high significance in random effects analysis of the entire genome in the studies of all ancestry groups, bringing the total number of susceptibility loci to 30 (24 in Europeans)”, explained Jordi Sunyer, researcher at CREAL, an ISGlobal allied center, researcher who has participated in this study. And continued “all newly identified susceptibility loci are related to (auto)immune regulation, in particular innate immune signaling and T cell activation and specification, and there appears to be a substantial geneticoverlap with other inflammatory and autoimmune diseases. Although not detracting from the importance of maintaining the skin barrier in the prevention and treatment of atopic dermatitis, our results support to new therapeutic approaches targeted at immune modulation”.

"It has been shown for the first time that genetic variants strongly associated with other autoimmune diseases were more likely to be associated nominally with atopic dermatitis" said Lavinia Paternoster, researcher at the Medical Research Council at the University of Briston (United Kingdom), and first author, along with Marie Standl, researcher at the Institute of Epidemiology in Munich (Germany).

Among others, have participated in this study Jordi Sunyer, Juan Ramón González, Mariona Bustamante and Natalia Vilor-Tejedor, researchers from CREAL, UPF and CIBERESP (CIBER in Epidemiology and Public Health). Bustamante is also researcher at the Centre for Genomic Regulation (CRG).